Selected-GenAtlas references	SOURCE	GeneCards	NCBI Gene	Swiss-Prot	Ensembl
	HGNC	UniGene	Nucleotide	OMIM	UCSC

Home Page

FLASH GENE

Symbol

CBLB

contributors: mct - updated : 24-06-2015

HGNC name	Cas-Br-M (murine) ecotropic retroviral transforming sequence b
HGNC id	1542

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Digestive mouth       highly Respiratory lung           respiratory tract trachea     highly

cells

System Cell Pubmed Species Stage Rna symbol Blood/Hematopoietic granulocyte

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

an UBA domain sufficient to confer the receptor trafficking functions of CBLB on CBL

HOMOLOGY

intraspecies

homolog to v-cbl proto-oncogene

Homologene

FAMILY

Cbl family of E3 ubiquitin (Ub) ligase

CATEGORY

protooncogene

SUBCELLULAR LOCALIZATION	plasma membrane
	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,nucleus,nucleoplasm

basic FUNCTION	functioning as a negative regulator of T-cell activation
	E3 ubiquitin ligase having a crucial role in the prevention of chronic inflammation and autoimmunity
	regulates the TLR4-mediated acute inflammatory response that is induced by sepsis
	both CBL and CBLB perform regulatory functions in osteoclasts that are unique to one or the other protein (i.e., functions that cannot be compensated by the other homolog)
	necessary role to prevent the inappropriate activation of NF-B in response to lipopolysaccharide and to polymicrobial sepsis
	involvement of CBLB in the regulation of osteoblast-related genes expression
	catalytic function of E3 ligase, CBLB, is essential for negative regulation of T cells
	plays a crucial role in T cell activation and tolerance induction
	essential and non-redundant role for CBLB in controlling TGFBR signaling by directly targeting SMAD7 for degradation during T cell responses
	is critical for establishing the threshold for T cell activation and is essential for induction of T cell anergy
	ubiquitin ligase (E3) that modulates signaling by tagging molecules for degradation
	is a type of E3 ubiquitin ligase that interacted with PTK2B, reduced the expression of PTK2B, and promoted trypsin-induced degradation of PTK2B
	role of CBLB in cell detachment
	acts as a scaffolding molecule to coordinate the delivery of the BCR and TLR9 into subcellular compartments required for productively delivering BCR-captured ligands to TLR9

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	potentially interacting with signal transduction molecules
	CBLB would control RUNX2 protein levels at the post-translational event
	inhibits T cell activation by suppressing PTEN
	inactivation independently of its ubiquitin ligase activity
	CLEC4G-mediated signaling up-regulates the threshold of CD4(+) T cell activation via tuning the expression of CBLB
	AKT2 but not AKT1 regulates FOXP3 expression downstream of CBLB
	CBLB, by promoting the ubiquitination and degradation of DDR2, functions as a negative regulator in the DDR2 signaling pathway
	is also required for entry of the Toll-like receptor 9 (TLR9) into late endosomes
	CBLB and CBL increased the protein level and stability of SIRT2 and CBLB and CBL interact with SIRT2
	NFKB1 downregulated CBLB by binding and suppressing CBLB promoter in T cell activation
	CBLB suppresses ORMDL3 expression through STAT6

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional         increases sepsis-induced release of inflammatory cytokines and chemokines constitutional       loss of function renders T cells hyperresponsive to antigenic stimulation and predisposes individuals toward developing autoimmunity

Susceptibility

to autoimmune diseases to type 1 diabetes in Japanese to multiple sclerosis

Variant & Polymorphism SNP , other	missense mutations of CBLB in Japanese subjects with type 1 diabetes
	T allele of rs9657904 within the CBLB gene significantly associated with multiple sclerosis (MS)

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology autoimmune   modulation of the E3 ligase activity of CBLB might be a novel modality to control T cell immunity in vaccination, cancer biology, or autoimmunity

ANIMAL & CELL MODELS

Cblb(-/-) mice are osteopenic, because of increased bone resorption with little compensating increase in bone formation